Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung.

Iodine 123 N-isopropyl-p-iodoamphetamine (123I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied 123I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of 123I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 x 64 matrix were obtained. The 123I-IMP clearance curve was described as follows: C(t) = A1e-k1t + A2e-k2t (A1, A2: intercepts, and k1, k2: slopes of the exponential components). 123I-IMP clearance was delayed in smokers, and k2 was smaller in smokers. Also, a correlation between k1, k2, and the number of cigarettes smoked per day was found (r = -0.65, r = -0.74, respectively, P less than 0.01). In conclusion, this study suggests that the delayed clearance and retention of 123I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.     

Effects of cigarette smoking on I-123 IMP clearance from the lung

N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the cigarette smoking on the uptake of IMP by the lung, we studied I-123 IMP clearance from the lung of 14 volunteers; 5 non-smokers and 9 smokers. After the injection of 111 MBq (3 mCi) of I-123 IMP into the medial cubital vein, the time-activity curve for 60 minutes and the regional activity using 1 frame per minute and a 64 x 64 matrix was obtained. I-123 IMP clearance curve was described as follows: C(t) = A1e-k1t + A2e-k2t (A1, A2: intercepts, and k1, k2: slopes of the exponential components). I-123 IMP clearance was delayed in smokers, and k2 was smaller in smokers. Also a significant correlations between k1, k2, and the number of cigarettes smoked per day were found. In conclusion, this study suggests that the delayed clearance and retention of I-123 IMP in the lung indicate the lung metabolic disorders due to cigarette smoking.     

123I-IMP accumulation in the lung with bronchial asthma--early uptake and delayed washout

123I-IMP is taken up by the pulmonary capillary endothelial cells during the first pass through the lung, and is slowly released from them. To look up the factors which influence on the prolonged 123I-IMP retention in the diseased lung, we examined the correlation between the 123I-IMP uptake during the first pass and the 123I-IMP retention. Patients with bronchial asthma had no abnormal finding in the chest X-ray photograph. However 123I-IMP release from their lungs was delayed. Some patients show a tendency that 123I-IMP uptake during the first pass was uneven, which suggested the change in amine uptake function of endothelial cells. However their correlation coefficients between the uptake during the first pass and the prolonged retention were very small. It was considered that the prolonged 123I-IMP retention in the diseased lung was not explained only by the change in uptake function of pulmonary capillary endothelial cell.     

Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung

Iodine 123 N-isopropyl p-iodoamphetamine (¹²³I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied ¹²³I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of ¹²³I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 × 64 matrix were obtained. The ¹²³I-IMP clearance curve was described as follows: C (t) = A ₁e^–k ₁ t+ A ₂e^–k ₂ t (A1, A ₂: intercepts, and k ₁, k ₂: slopes of the exponential components). ¹²³I-IMP clearance was delayed in smokers, and k ₂ was smaller in smokers. Also, a correlation between k ₁, k ₂, and the number of cigarettes smoked per day was found (r = –0.65, r = –0.74, respectively, P<0.01). In conclusion, this study suggests that the delayed clearance and retention of ¹²³I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.Offprint requests to: K. Kato     

Prolonged lung retention of123I-IMP in pulmonary fibrosis

We compared radiographic findings and the retention of N-isopropyl- p[123I]-iodoamphetamine (123I-IMP) in 23 patients with pulmonary fibrosis. During the 30 minutes following a rapid injection of 55.5 MBq of 123I-IMP into the antecubital vein, the image of regional activity was stored. After this, 185 MBq of 99mTc-MAA was injected and its image was stored to determine the region of interest. The half time (T1/2) of 123I-IMP release from the lung was calculated in each pixel between 10 and 25 minutes after the injection. Chest roentgenograms were taken, and the lung field was divided into 6 portions (right upper, middle and lower, and left upper, middle and lower). A quantitative score was assigned to the radiographic finding (X-ray score). The T1/2 values in the above patients were longer than the T1/2 values in normal subjects. Prolonged T1/2 values were observed in the lung fields which had high X-ray scores. The X-ray scores and the T1/2 values in corresponding areas had a positive relation.     

Prolonged lung retention of 123I-IMP in pulmonary disease

The accumulation of venously injected 123I-IMP in the lung was studied. Between 30 and 50 min after the injection of the 1.5 mCi 123I-IMP, the concentration of 123I-IMP in the broncho-alveolar lavage fluid were much higher than in the blood. It was considered that 123I-IMP was transported into the alveolar spaces and was absorbed by the alveolar cells. The half time (T1/2) of the 123I-IMP release from the lung between 10 and 25 min immediately after the injection was calculated. In normal subjects the T1/2 ranged between 25 and 44 min and was prolonged in subjects with pulmonary fibrosis, sarcoidosis, and allergic alveolitis. It was considered that the retention of 123I-IMP was related not only to the endothelial cells, but also to the alveolar cells. It was considered that the analysis of the lung release of 123I-IMP forms a new lung dysfunction index.     

Clinical and experimental studies on the mechanism of abnormal accumulation in lung scanning with 123I-IMP.

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.     

Evaluation of delayed I-123 IMP lung studies in atelectatic and inflammatory diseases in comparison with Ga-67-citrate scintigraphy

We have previously reported that increased tracer accumulation on delayed 123I-IMP scintigraphy is associated with atelectasis and inflammation. The purpose of this study was to evaluate the diagnostic values of delayed 123I-IMP lung scintigraphy, compared with gallium scintigraphy. Ten patients with atelectasis caused by lung cancer and 7 patients with inflammatory diseases were studied. Inflammatory lung disease included 4 cases of pneumonia, 2 of interstitial pneumonitis, and 1 of diffuse panbronchiolitis. Delayed 123I-IMP scintigraphy was performed 24 hours after intravenous injection of 111 MBq of 123I-IMP. In 14 patients, the SPECT images were obtained. Gallium scintigraphy was done within 7 days of 123I-IMP scintigraphy and the images were obtained 72 hours after the administration of 111 MBq of 67Ga-citrate. 123I-IMP scintigraphy was compared with gallium scintigraphy for its ability to detect atelectasis. The degree of uptake by the collapsed lobes was judged visually on planar images and rated using four grades: negative, slight, moderate and heavy. All the cases showed moderate or intense uptake on the 123I-IMP images, whereas with gallium scintigraphy there was no change corresponding with lobar collapse in 8 out of 10 cases. Of the remaining 2 cases, one had tumor in the collapsed lobe and the other had obstructive pneumonia. In inflammatory lung diseases, the correlation of 123I-IMP and gallium images regarding degree of change shown on chest X-ray film was studied. The degree of correlation was classified using four grade: poor, fair, good and excellent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differentiation of infiltrates between lung cancer and noncancerous lung disease by 123I-IMP lung imaging

Lung imaging with N-isopropyl-p-123I-iodoamphetamine (123I-IMP) was performed to estimate the pulmonary lesion imaging findings in 3 patients with bronchogenic carcinoma (2: bronchioloalveolar carcinoma and 1: adenocarcinoma) and 18 with noncancerous lung diseases (10: bacterial pneumonia, 1: viral pneumonia, 1: aspiration pneumonia, 1: radiation pneumonitis, 4: pulmonary tuberculosis and 1: obstructive pneumonitis due to an endobronchial lipoma) at 30 min and 4 hr after i.v. injection of 111 MBq of 123I-IMP. These patients all exhibited infiltrates only in the chest radiograms. Decreased uptake of 123I-IMP was observed in the cancerous infiltrating lesions in 3 patients with bronchogenic carcinoma at 30 min and 4 hr, while the uptake of 123I-IMP was normal or increased at 30 min and intense at 4 hr in all 18 noncancerous infiltrating lesions. Therefore 123I-IMP lung imaging can be used to differentiate bronchogenic carcinoma from noncancerous lung disease in patients who exhibit infiltrates only in the chest radiograms.     

Prolonged lung retention of 123I-IMP in pulmonary disease

The accumulation of venously injected ¹²³I-IMP in the lung was studied. Between 30 and 50 min after the injection of the 1.5 mCi ¹²³I-IMP, the concentration of ¹²³I-IMP in the broncho-alveolar lavage fluid were much higher than in the blood. It was considered that ¹²³I-IMP was transported into the alveolar spaces and was absorbed by the alveolar cells. The half time (T _1/2) of the ¹²³I-IMP release from the lung between 10 and 25 min immediately after the injection was calculated. In normal subjects the T _1/2 ranged between 25 and 44 min and was prolonged in subjects with pulmonary fibrosis, sarcoidosis, and allergic alveolitis. It was considered that the retention of ¹²³I-IMP was related not only to the endothelial cells, but also to the alveolar cells. It was considered that the analysis of the lung release of ¹²³I-IMP forms a new lung dysfunction index.     

SPECT images after intravenous injection of 99mTc-DTPA in lung tumors--comparison with delayed 123I-IMP lung scintigraphy

The aim of this study was to assess the efficacy of SPECT imaging of the thorax with 99mTc-DTPA, which accumulates at sites of increased capillary permeability and expanded extracellular space, by comparing it with delayed 123I-IMP lung scintigraphy. We have previously reported that increased uptake on delayed 123I-IMP lung scintigraphy was associated with atelectasis and inflammation. Thirteen patients with lung cancer (4 with atelectasis and 3 with pleurisy), one patient with malignant lymphoma complicated by pneumonia and pleurisy, and one patient with pneumonia were studied. 99mTc-DTPA scintigraphy was performed twice, 20-160 minutes and 2-4 hours after the intravenous administration of 370 MBq of 99mTc-DTPA. 123I-IMP scintigraphy was performed 24 hours after the intravenous injection of 111 MBq of 123I-IMP. SPECT images were obtained with both types of scintigraphy. 99mTc-DTPA scintigraphy was compared with 123I-IMP scintigraphy for its ability to detect atelectasis and pneumonia. All patients showed increased accumulation corresponding to the lesions on both 123I-IMP and 99mTc-DTPA scintigraphy. 123I-IMP scintigraphy showed a defect corresponding to the tumor with increased accumulation around the tumor, whereas 99mTc-DTPA scintigraphy showed accumulation corresponding to the tumor. Ten of 11 tumors showed accumulation of an intensity equal to that of the soft tissue of the chest wall on 20-60 min 99mTc-DTPA images. The 2-4 hr images showed that 99mTc-DTPA leaked from the periphery of the tumor toward its center. All the patients with pleurisy showed increased accumulation in effusion on 2-4 hr 99mTc-DTPA scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of increased 123I-IMP uptake in adenocarcinoma of the lung

It has been reported that delayed 123I-IMP lung scintigraphy shows a defect corresponding to the tumor with increased accumulation around the tumor, and that an increased accumulation is associated with atelectasis and inflammation. We presented a case of increased uptake of 123I-IMP in lung cancer. None of the other reported case of increased uptake in lung cancer, to our knowledge, occurred. A 55-year-old man had a 6 cm mass in the lower lobe of the right lung. Cytologic examination with a small curette diagnosed the case as an adenocarcinoma. The 123I-IMP scintigraphy was performed 24 hours after intravenous injection of 111 MBq of 123I-IMP. The 123I-IMP SPECT lung images showed an area of increased 123I-IMP concentration corresponding to the tumor mass. The patient's subsequent course was characterized by massive pleural effusion caused by extensive invasion to the pleura despite chemotherapy. He died about 2 months after the 123I-IMP scintigraphy. The right lung removed at necropsy confirmed that the area of high 123I-IMP concentration corresponded to the mass, which proved a poorly differentiated adenocarcinoma. One should note that there is an unusual case with high 123I-IMP uptake in lung cancer.     

Evaluation of the 123I-IMP Patlak plot method using the pulmonary differential curve as an input function: a comparison with cerebral blood flow (CBF) determined by the noninvasive micro-sphere (NIMS) method

We explored the possibility of applying the Patlak plot method to clinical practice as a simple non-invasive quantitative method of measuring cerebral blood flow using N-isopropyl-4-[123I]iodoamphetamine (123I-IMP). On the assumption that after temporarily accumulating in the lungs, all the administered 123I-IMP is eliminated by the pulmonary arterial flow for systemic diffusion, we collected dynamic data by setting an area ranging from the brain to the whole lung field within the field of the camera. The lung clearance curve L(t) was differentiated and divided by cardiac output. It was then converted a positive number by multiplying it of--1 to determine the volume of 123I-IMP tracer diffused in arterial blood per unit of time. The calculated concentration was defined as the arterial time activity curve A(t). A Patlak plot analysis was conducted between A(t) and the brain time activity curve B(t) to determine K1 (total cerebral blood flow [tCBF], ml/min) and Vn (nonspecific initial distribution volume, ml). The total volume of tracer diffused in the central cardiovascular system within a given (T) was also obtainer from the volume of tracer remaining in the lungs [Lpeak--L(T)], and by reporting this calculation over time, an accumulation curve was produced. By differentiating the obtained accumulation curve, we were able to estimate the volume of tracer diffused in the central cardiovascular system per unit of time. With this value used as the input function index I(t), a Patlak plot analysis was conducted to determine the unidirection influx index ki, which was then multiplied by 100 to obtain the brain perfusion index (IMP-BPI). The noninvasive micro-sphere method was performed concurrently on 16 patients with cerebrovascular and/or neurological disorders to obtain mean cerebral blood flow (mCBF). Correlations between K1 and between IMP-BPI and mCBF were then determined and compared. Both K1 and IMP-BPI obtained from ki were found to correlate highly with mCBF, r = 0.759 (y = 0.032x + 20.1) and r = 0.833 (y = 2.73x + 0.10) respectively, with a better result from IMP-BPI. These results indicate that the 123I-IMP Patlak plot method with a wide-field gamma camera is clinically applicable as a simpler noninvasive technique for measuring cerebral blood flow even when a simple input function is used.     

Visualization of functional improvement by 123I-IMP lung SPET after thromboendarterectomy for chronic pulmonary embolism

We report on six patients with chronic pulmonary embolism who underwent 123I-IMP and 99Tcm-MAA lung SPET before and after thromboendarterectomy. 123I-IMP lung SPET can assess the viability of lung parenchyma, because it is a non-particulate agent that accumulates in the endothelial membranes of pulmonary capillaries. Chronic pulmonary thromboembolism accompanied by pulmonary hypertension has a poor prognosis that may be improved only by thromboendarterectomy. We compared 123I-IMP and 99Tcm-MAA lung SPET in terms of functional improvement after such surgery. After thromboendarterectomy, all six patients were functionally improved, according to the criteria of the New York Heart Association. The pre- and post-surgery percentage of vascular obstruction did not differ significantly with 99Tcm-MAA lung SPET (44.8 +/- 11.2% and 32.5 +/- 15.6% pre- and post-surgery, respectively). In contrast, 123I-IMP lung SPET revealed a significant pre- versus post-surgery difference (15.5 +/- 9.5% and 3.3 +/- 5.9% pre- and post-surgery, respectively). 123I-IMP lung SPET could be useful for evaluating thromboendarterectomy because pulmonary parenchymal viability owing to arterial microvasculature can be estimated.     

A noninvasive assessment of pharmacological interaction of amines in the lung

Lung endothelial binding sites of N-isopropyl-123I-p-iodoamphetamine (123I-IMP) were assessed employing the principle of competitive binding assay adapted for in vivo measurement using a computer-scintillation camera technique. A noninvasive modification of the Chinard-Crone technique was applied to the study of pulmonary extraction. 123I-IMP, the test cellular tracer and 99Tcm-dextran the vascular reference tracer were used in dogs to determine the first pass pulmonary extraction of 123I-IMP. The lung extraction of 123I-IMP decreases progressively from 90 to 62% as the amount of propranolol (administered 10 min prior to the injection of 99Tcm-dextran) gradually increased from 0 to 20 mg. The dissociation constant of 123I-IMP lung binding sites reaction in the presence of propranolol was calculated by Scatchard plot and found to be 10 mg. The in vivo procedure described in this paper will enable us to develop a model for the assay of the binding sites in the lungs for amine and its influence in both health and disease.     

Evaluation of lung scintigraphy using N-isopropyl-p-[123I]-iodoamphetamine

N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) was examined for its relevancy as a labeling medium of lung scintigraphy in 30 patients with lung diseases and 20 healthy subjects. Lung diseases were classified into carcinoma and diffuse lung disease, and the all subjects with normal lung were classified into smokers and nonsmokers. To assess the reduction curve of 123I-IMP, mean transit time was calculated. Forced spirography was performed and spirographic values were analyzed. Spirographic parameters examined were vital capacity percent (%VC), forced expiratory volume in 1 sec divided by forced vital capacity (%) (FEV1.0%), and blood gas data. In the correlation matrix, the mean transit time was correlated with blood gas data, and not with %VC or FEV1.0%. In patients with lung diseases, the mean transit time was significantly prolonged; however, the difference was not significant between groups of carcinoma and benign disease, and between groups of smokers and nonsmokers. Wash-out images were obtained by the subtraction technique using the first frame image and 100-min delayed image. In patients with lung carcinoma, 87.5% of the tumors were depicted on wash-out images. The lesions were also depicted well in benign lung diseases. But among findings of wash-out image by 123I-IMP, air trapping image by 133Xe study and XCT study, there are some discordances to be clarified.     

Experimental study on the mechanism of the intrapulmonary kinetics of 123I-IMP in a balloon occluded bronchus in rabbits

To investigate the mechanism of intrapulmonary kinetics of N-isopropyl-p-123I-iodoamphetamine (123I-IMP), we performed lung scanning with 123I-IMP in 13 rabbits in which a unilateral bronchus was occluded by a balloon catheter. In 9 rabbits, on the delayed distribution images, an abnormal accumulation of 123I-IMP was detected in the hypoperfusion area of the peripheral lung field of the occluded bronchus, which was detected on lung perfusion images with 99mTc-MAA. Comparison of early (a summation image during 20 seconds immediately after injection) and delayed (a summation image from 70 to 90 minutes after injection) distribution images confirmed that during this period, 123I-IMP accumulated in the area of reduced distribution of 123I-IMP. Moreover, at the site of abnormal accumulation, washout of 123I-IMP from the lung was delayed compared with that in the normal lung field. We find this experimental study is similar to the results in 63 clinical cases, which we have reported previously, and confirm that pulmonary arterial perfusion, especially hypoperfusion, influences the intrapulmonary kinetics of 123I-IMP.     

Experimental study on 123I-IMP kinetics in irradiated lung of rabbit]

Radiation-induced alteration of intra-pulmonary kinetics of 123I-IMP was investigated in 11 rabbits received a 50 Gy dose of radiation to the hemithorax. In all of these rabbits examined during 3-17 weeks following the irradiation, an abnormal accumulation was seen in the irradiated lung on the delayed image obtained 60 minutes after the injection of 123I-IMP. The time-activity curves in the irradiated lung following the injection had shallower downslopes of both the initial fast phase and the following slow phase than those of non-irradiated lung, and finally 123I-IMP uptake of the irradiated lung exceeded that of the normal lung. Chest radiographies all of 11 rabbits showed no abnormal shadow and histological studies in 6 of them revealed a relatively slight change or injury of the irradiated lung during 3-17 weeks. These results indicate that this agent may be useful for detecting and assessing relatively early and slight lung injury induced by irradiation.     

Altered kinetics of 123I-IMP in irradiated rabbit lungs.

Radiation-induced alteration of intrapulmonary kinetics of 123I-IMP was investigated in 11 rabbits receiving a 50 Gy dose of radiation to one lung. In all 13 examinations of these rabbits, 3-17 weeks following radiation, the delayed images of 123I-IMP lung scintigrams showed abnormal accumulation in the irradiated lungs. The time-activity curves of the irradiated lung following injection of 123I-IMP had shallower downslopes of both the initial fast phase and the following slow phase than those of the non-irradiated lung. Finally the radioactivity of the irradiated lung exceeded that of the normal lung. The altered intrapulmonary kinetics of 123I-IMP in the irradiated lung was clearly confirmed. 99Tcm-MAA lung perfusion scintigrams showed reduced uptake in the irradiated lungs; the uptake decreased with time following radiation. Pulmonary arterial perfusion was considered to influence the distribution and kinetics of 123I-IMP, however, those of 123I-IMP did not reflect only the pulmonary arterial perfusion observed by 99Tcm-MAA scintigrams. Chest radiography and histological studies revealed a relatively slight change or injury of the irradiated lung in these rabbits. These results indicate that this agent could be useful in detecting and assessing early lung injury induced by radiation, and will give us pathological information in addition to lung perfusion in the peripheral area where the large 99Tcm-MAA molecule cannot reach.     

Evaluation of the lung uptake of 123I-IMP by bronchoalveolar lavage

A 67-year-old female with radiation pneumonitis in the right upper lobe underwent lung scanning and bronchoalveolar lavage 4 hours after the intravenous injection of 123I-IMP. The lung scanning showed increased accumulation of 123I-IMP, corresponding with the area of radiation pneumonitis. The ratios of radioactivities of the cellular and noncellular components in the bronchoalveolar lavage fluid to that of the serum, were 27.0 and 0.39, respectively. Our results suggest that 123I-IMP or its metabolites are transported through alveolo-capillary barrier and taken up by free cells in the alveolar space after 123I-IMP has been bound to nonspecific receptor sites in the endothelial cell in the capillary lumen.